Tumor necrosis factors generally called TNF (typically three types, namely TNF-α, TNF-β (LT-α), LT-β) are cytokines that are produced primarily in immune system cells. TNF-α being representative thereof is produced mainly in macrophages and shows various physiological activities such as small thrombi formation and apoptosis induction, etc. Excessive production (expression) of TNF-α is known to bring on diseases such as rheumatoid arthritis and the like.
As for the receptors to which such TNF binds, there are a type 1 TNF receptor (tumor necrosis factor receptor 1 or “TNF-R1” hereinafter) having a molecular weight of about 55 kDa and a type 2 TNF receptor (tumor necrosis factor receptor 2 or “TNF-R2” hereinafter) having a molecular weight of about 75 kDa.
These two types of TNF receptor are known to give rise to different, individual physiological effects. It is reported, for instance, that in a test with TNF-R1 knockout mice and TNF-R2 knockout mice, arteriogenesis of the upper limb and angiogenesis of the lower limb are enhanced in TNF-R1 knockout mice, but are impaired in TNF-R2 knockout mice (Non-Patent Document 1). It has also been reported that the progress of glaucoma is slower in TNF-R2 knockout mice than in wild-type mice (oral presentation by S. McKinnon et al., “Neuroinflammation in Glaucoma” at XIX Biennial Meeting of the International Society for EYE RESEARCH, Jul. 18-23, 2010). It is also reported that photoreceptor degeneration induced by retinal detachment is mediated by TNF-α acting via TNF-R2, but not much affected by TNF-R1 deficiency (Non-Patent Document 2).